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A Genetic Linkage Study of the D2 Dopamine Receptor Locus in Heavy Drinking and Alcoholism

  • C. C. H. Cook (a1), G. Palsson (a2), A. Turner (a3), D. Holmes (a4), P. Brett (a5), D. Curtis (a6), H. Petursson (a7) and H. M. D. Gurling (a3)...



Reports of an association between restriction fragment length polymorphisms (RFLPs) at the dopamine D2 receptor (DRD2) locus and alcoholism have suggested involvement of that locus in the aetiology of alcoholism.


Sib pair linkage analyses were conducted in families multiply affected by alcoholism, using both the Taql ‘A’ RFLP and a microsatellite repeat polymorphism at the DRD2 locus.


The ‘Identical By Descent’ analysis provided significant evidence of an effect of the DRD2 locus on the liability to develop heavy drinking (P<0.0016) and Research Diagnostic Criteria alcoholism (P<0.0003) in the first sample of families studied. However, this result was explicable by the segregation of alleles in a single large sibship, and it was not replicated in a second sample of families.


The results do not support linkage between the DRD2 locus and alcoholism in most of the families studied. It remains possible that this locus influences the predisposition to alcoholism in some families.


Corresponding author

Dr C. Cook, Consultant and Senior Lecturer in the Addictions, National Addiction Centre, 4 Windsor Walk, London SE5 8AF


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Blum, K., Noble, E. P., Sheridan, P. J., et al (1990) Allelic association of human dopamine D2 receptor gene in alcoholism. Journal of the American Medical Association, 263, 20552060.
Bolos, A. M., Dean, M., Lucas-Derse, S., et al (1990) Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. Journal of the American Medical Association, 264, 31563160.
Caetano, R., Edwards, G., Oppenheim, A. N., et al (1978) Building a standardised alcoholism interview schedule. Drug and Alcohol Dependence, 3, 185197.
Comings, D. E., Comings, B. G., Muhleman, D., et al (1991) The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. Journal of the American Medical Association, 266, 17931800.
Cook, C. C. H. & Gurling, H. M. D. (1990) The genetic aspects of alcoholism and substance abuse: a review. In The Nature of Drug Dependence (eds Edwards, G. & Lader, M.), pp. 75 111 Oxford: Oxford University Press.
Cook, C. C. H. & Gurling, H. M. (1994) The D2 dopamine receptor gene and alcoholism: a genetic effect in the liability for alcoholism. Journal of the Royal Society of Medicine, 87, 400402.
Cook, , Brett, P., Curtis, D., et al (1993) Linkage analysis confirms a genetic effect at the D2 dopamine receptor locus in heavy drinking and alcoholism. Psychiatric Genetics, 3, 130.
Edwards, G. & Gross, M. (1976) Alcohol dependence: provisional description of a clinical syndrome. British Medical Journal, 1, 10581061.
Finckh, U., Giraldo-Velasquez, M., Otto, G., et al (1995) Phytogeny of the human dopamine D2 receptor gene (DRD2) and investigation of its association with alcoholism. Psychiatric Genetics, 5(supplement 1), S77.
Gejman, P. V. (1993) No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Psychiatry and Genetics, 3, 130131.
Gelernter, J., Goldman, D. & Risch, N. (1993) The A1 allele at the D2 dopamine receptor gene and alcoholism. A reappraisal. Journal of the American Medical Association, 269, 16731677.
Goldin, L. R., Clerget-Darpoux, F. & Gershon, E. S. (1982) Relationship of HLA to major affective disorder not supported. Psychiatry Research, 7, 2945.
Grandy, D. K., Litt, M., Allen, L., et al (1989) The human dopamine D2 receptor gene is located on chromosome 11 at q22–q23 and identifies a TaqI RFLP. American Journal of Human Genetics, 45, 778785.
Hauge, X. Y., Grandy, D. K., Eubanks, J. H., et al (1991) Detection and characterisation of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics, 10, 527530.
Hodge, S. W. (1984) The information contained in multiple sibling pairs. Genetic Epidemiology, 1, 109122.
Neiswanger, K., Hill, S. Y. & Kaplan, B. B. (1995) Association and linkage studies of the TaqI A1 allele at the dopamine D2 receptor gene in samples of female and male alcoholics. American Journal of Medical Genetics, 60, 267271.
Noble, E. P. (1993) The D2 dopamine receptor gene: a review of association studies in alcoholism. Behavior Genetics, 23, 119129.
Parsian, A., Todd, R. D., Devor, E. J., et al (1991) Alcoholism and alleles of the human D2 dopamine receptor locus. Archives of General Psychiatry, 48, 655663.
Royal College of Psychiatrists (1986) Alcohol: Our Favourite Drug. London: Tavistock.
Sandkuyl, L. A. (1989) Analysis of affected sib pairs using information from extended families. In Multipoint Mapping and Linkage Based upon Affected Pedigree Members (eds Elston, R. C., Spence, M. A., Hodge, S. E., et al), pp. 117122. New York: Alan R. Liss.
Skinner, H. A. & Sheu, W.-J. (1982) Reliability of alcohol use indices: the lifetime drinking history and the MAST. Journal of Studies on Alcohol, 43, 11571170.
Smith, S. S., Ohara, B. F., Persico, A. M., et al (1992) Genetic vulnerability to drug abuse. Archives of General Psychiatry, 49, 723727.
Southern, E. M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. Journal of Molecular Biology, 98, 503517.
Spitzer, R. L. & Endicott, J. (1979) Schedule for Affective Disorders and Schizophrenia – Lifetime Version (3rd edn). New York: New York State Psychiatric Institute.
Spitzer, R. L. & Robins, E. (1978) Research diagnostic criteria. Archives of General Psychiatry, 35, 773782.
Suarez, B. K. & Hodge, S. E. (1979) A simple method to detect linkage for rare recessive disease: an application to juvenile diabetes. Clinical Genetics, 15, 126136.
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A Genetic Linkage Study of the D2 Dopamine Receptor Locus in Heavy Drinking and Alcoholism

  • C. C. H. Cook (a1), G. Palsson (a2), A. Turner (a3), D. Holmes (a4), P. Brett (a5), D. Curtis (a6), H. Petursson (a7) and H. M. D. Gurling (a3)...
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